Synthesis, Biological Validation, and Docking Studies of Novel Purine Derivatives Containing Pyridopyrimidine, Pyrazolopyridine, and Pyranonapthyridine Rings^†

Abstract

New strategy for the synthesis of 2-(2,3,6,9-tetrahydro-1,3-dimethyl-2,6-dioxo-1H-purin-8-yl)acetonitrile through a molecular linking with pyridopyrimidine, pyrazolopyridine, and pyranonapthyridine derivatives. The newly synthesized compounds were characterized on the basis of spectral (FT-IR, ¹H, ¹³C NMR, Mass spectral) analyses and further screened for their antimicrobial, antioxidant, and anticancer properties. Compound 6a indicated a higher activity against Gram-negative bacteria and compound 7d toward Gram-positive bacteria. Antifungal validation of the compounds revealed 7b as sensible against Aspergillus niger, Aspergillus oryzae, Candida albicans, and Penicillium chrysogenum at all concentrations. Compound 6b showed prominent cytotoxic activity with IC₅₀ (µM) values of 0.8 ± 0.61, 1.0 ± 0.3, 1.2 ± 0.7, and 0.90 ± 0.71 against MCF-7, A-549, HeLa, and Panc-1 cancer cell lines, respectively. Compounds 6c and 10c showed significant antioxidant activity at all concentrations with ED₅₀ values (3.39 ± 0.3 and 4.27 ± 0.5 μM, respectively). Further, docking was performed at the 1SA5 active site to anticipate their conceivable binding mode by compound 6b.

Graphical Abstract

Keywords:

• Anticancer
• pyridopyrimidine
• pyrazolopyridine
• pyranonapthyridine
• 1SA5

Acknowledgements

The authors are thankful to the Principal, Shri Prabhu Arts, Science and J.M. Bohra Commerce, Degree College Shorapur, Yadgir, Karnataka, India for provide laboratory facilities. Authors are grateful to the Directors, IIT Madras, Chennai, India provide spectral data, National Collection of Industrial Microorganisms (NCIM), National Chemical Laboratory (NCL), and National Centre for Cell Science (NCCS), Pune, India to providing test materials.

Conflict of interest

The authors declare that no conflict of interest.